In order to develop rational bases for treatment of hearing disorders, four institutions of the greater Boston area have joined in forming a multidisciplinary group to conduct research on the physiological mechanisms that operate in vertebrate hearing. Five stages of the system are defined for study: 1.) The middle-ear which transmits sound from the external to the inner ear. Measurements of physical variables such as sound pressure, ossicular movement, acoustic input impedance to the cochlea are made in selected vertebrates. Mathematical models for sound transmission through the middle ear are generated from these data and effects of the middle-ear muscle contractions are explored; 2.) The cochler where transduction of accoustic stimuli to neural activity occur. The relationship of auditory-nerve fiber responses to the morphology of the hair cells innervated and the peripheral innervation pattern will be studied by intracellularly marking physiologically identified fibers in the lizard cochlea. The chemical nature of the hair-cell transmitter(s) will be studied with the aid of bioassays sensitive to extracts of fish organs rich in hair cells; 3.) The auditory nerve which provides the input to the brain from the ear. The coding of speech information will be addressed by recording from myelinated fibers in the auditory nerve of anesthetized cats. Recordings from spiral ganglion neurons giving rise to the small, unmyelinated fibers in the auditory nerve will be attempted in guinea pigs; 4.) The cochlear nucleus is the first auditory nucleus in the brain. The central projections and connections of the unmyelinated fibers in the auditory nerve will be followed as they ramify in the cochlear nucleus of adult cats. The gross distribution of the endings from the unmyelinated fibers and the morphology of the parent cell bodies will be explored by immunological methods; and 5.) The central neural pathways that provide the neuronal circuitry in the brain for processing auditory signals. Two feedback mechanisms will be studied. The first is the middle-ear-muscle reflex pathway, which will be defined and studied in cats. The second is the cochlear efferent supply, which will be examined in surgical patients by testing physiological responses and psychophysical performance in humans before and after the olivocochlear bundle is cut. In another set of studies, binaural perception will be related to evoked potentials in man.